Inbreeding and loss of genetic variation are considered to be major threats to small and endangered populations. The reduction of fitness due to inbreeding is believed to be more severe under stressful environmental conditions. We generated nine strains of the ecotoxicological model organism Chironomus riparius of different inbreeding levels in order to test the hypothesis that the inbreeding level and thus the degree of genome-wide homozygosity influences the life-history under cadmium exposure. Therefore, midge populations were exposed to a gradient of sediment-bound cadmium. The level of genetic variation in the used strains was assessed using microsatellite markers. In the life-cycle tests, inbreeding reduced fitness within C. riparius populations both under control and stressed conditions. However, differences between genetically diverse and impoverished strains were greatest at high cadmium exposure. Overall, inbreeding effects were not only dependent on cadmium concentrations in the sediment, but also on the life-history trait investigated. While some parameters where only affected by inbreeding, others were altered by both, inbreeding and cadmium. For the larval developmental time, a significant interaction was found between inbreeding and cadmium stress. While all strains showed a similar developmental time under control conditions, high rates of inbreeding led to a significantly delayed emergence time under high cadmium concentrations, resulting in longer generation periods and reduced population growth rates as population-relevant effects. The results show, that bioassays with C. riparius are affected by the level of inbreeding within Chironomus test strains. Pollution stress is therefore likely to affect the survival of rare and endangered populations more severe than that of large and genetically diverse ones.